Particle beam liquid chromatography mass spectrometry (PB LC/MS) is a relatively new analytical technique. In prior art PB LC/MS systems, an aerosol consisting of helium dispersion gas and droplets containing relatively low levels of analyte dissolved in LC effluent is first generated by a nebulizer. The aerosol is injected into a heated desolvation chamber where the volatile components of the droplets (primarily HPLC effluent) are vaporized, resulting in a mixture of helium gas, solvent vapor, and desolvation solvent particles. This mixture then enters a two stage momentum separator in which the less massive components (such as solvent vapor and helium gas) are pumped away while the more massive particles continue through the system on, what was believed to be, a more or less
2 straight line into the mass spectrometer source where the particles are vaporized, ionized, and mass analyzed. The momentum separator also serves as a pressure reduction and sample enrichment device, since most of the gas and solvent are pumped away, while most of the sample enters the mass spectrometer.
Browner et al., U.S. Pat. No. 4,629,478, issued Dec. 16, 1986, purports to describe a monodisperse aerosol generator which forms a stable jet of liquid at a velocity which allows columnar breakup into droplets of uniform size and spacing. Brandt et al , U.S. Pat. No. 4,863,491, issued Sep. 5, 1989, describes a multistage particle beam separator.
One problem encountered in the first generation of PB LC/MS instruments is poor linear response. Recent publications have shown that there is a systematic non-linearity in current instruments. See McLaughlin et al., "Particle Beam LC/MS for Drug Testing: Influence of Carrier Effect on Quantitation," paper 227, 6th (Montreux) Symposium on Liquid Chromatography/Mass Spectrometry; Behymer et al., "Liquid Chromatography/Particle Beam/Mass Spectrometry of Polar Components of Environmental Interest," Anal. Chem., 62, 1990, 1686-1690; and Bellar et al., "Investigation of Enhanced Ion Abundances from a Carrier Process in High Performance Liquid Chromatography Particle Beam Mass Spectrometry," J. Am. Soc. Mass Spectrom., 1, 1990, 92-98. Bellar and Behymer have referred to the problem as a "carrier effect" because the phenomena can also be seen as enhanced ion abundances in the presence of co-eluting components. This is the same as non-linearity, since non-linear behavior is a kind of self-carrier effect. These researchers have observed that by deliberately adding buffer to the mobile phase, a constant "co-eluting" component, the carrier effect is reduced and the linearity improves.